Arteriolar neuropathology in cerebral microvascular disease.

Cerebral microvascular disease (MVD) is an important cause of vascular cognitive impairment. MVD is heterogeneous in aetiology, ranging from universal ageing to the sporadic (hypertension, sporadic cerebral amyloid angiopathy [CAA] and chronic kidney disease) and the genetic (e.g., familial CAA, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy [CADASIL] and cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy [CARASIL]). The brain parenchymal consequences of MVD predominantly consist of lacunar infarcts (lacunes), microinfarcts, white matter disease of ageing and microhaemorrhages. MVD is characterised by substantial arteriolar neuropathology involving ubiquitous vascular smooth muscle cell (SMC) abnormalities. Cerebral MVD is characterised by a wide variety of arteriolar injuries but only a limited number of parenchymal manifestations. We reason that the cerebral arteriole plays a dominant role in the pathogenesis of each type of MVD. Perturbations in signalling and function (i.e., changes in proliferation, apoptosis, phenotypic switch and migration of SMC) are prominent in the pathogenesis of cerebral MVD, making 'cerebral angiomyopathy' an appropriate term to describe the spectrum of pathologic abnormalities. The evidence suggests that the cerebral arteriole acts as both source and mediator of parenchymal injury in MVD.

Regional Cerebral Small Vessel Disease (rCSVD) Score: A clinical MRI grading system validated in a stroke cohort.

BACKGROUND: Current methods for quantitative assessment of cerebral small vessel disease (CSVD) ignore critical aspects of the disease, namely lesion type and regionality. We developed and tested a new scoring system for CSVD, "regional Cerebral Small Vessel Disease" (rCSVD) based on regional assessment of magnetic resonance imaging (MRI) features. METHODS: 141 patients were retrospectively included with a derivation cohort of 46 consecutive brain MRI exams and a validation cohort of 95 patients with known cerebrovascular disease. We compared the predictive value of rCSVD against existing scoring methods. We determined the predictive value of rCSVD score for all-cause mortality and recurrent strokes. RESULTS: 46 (44 male) veteran patients (age: 66-93 years), were included for derivation of the rCSVD score. A non-overlapping validation cohort consisted of 95 patients (89 male; age: 34-91 years) with known cerebrovascular disease were enrolled. Based on ROC analysis with comparison of AUC (Area Under the Curve), "rCSVD" score performed better compared to "total SVD score" and Fazekas score for predicting all-cause mortality (0.75 vs 0.68 vs 0.69; p = 0.046). "rCSVD" and total SVD scores were predictive of recurrent strokes in our validation cohort (p-values 0.004 and 0.001). At a median of 5.1 years (range 2-17 years) follow-up, Kaplan-Meier survival analysis demonstrated an rCSVD score of 2 to be a significant predictor of all-cause-mortality. CONCLUSION: "rCSVD" score can be derived from routine brain MRI, has value in risk stratification of patients at risk of CSVD, and has potential in clinical trials once fully validated in a larger patient cohort.

A Positive Association between the Atherogenic Index of Plasma and White Matter Hyperintensity.

BACKGROUND: White matter hyperintensity (WMH) is a risk factor for dementia and ischemic stroke. The atherogenic index of plasma (AIP) is a simple and cost-effective marker for the prediction of various vascular diseases. In this study, we evaluated the relationship between AIP and WMH in adults without cerebrovascular accidents. METHODS: We analyzed the data of 281 adults, aged ≥26 years, who underwent brain magnetic resonance imaging (MRI) at the health promotion center of an education hospital between January 2014 and December 2018. Participants were divided into three categories according to tertiles of the AIP scores (T1: <0.20; T2: 0.20-0.48; and T3: >0.48). WMH was defined as a modified Fazekas scale score of 1-3 on brain MRI. A cubic spline curve was used to determine the linearity of the relationship between AIP and WMH. Multiple logistic regression analysis was used to evaluate the relationship between the AIP and WMH. RESULTS: The prevalence of WMH was 45.7% in T1, 57.0% in T2, and 66.0% in T3 (T3 vs. T1, P for post-hoc analysis=0.005). The increased odds of WMH were associated with increased AIP. The odds ratio (OR) with a 95% confidence interval (CI) for WMH of T2 and T3 compared with T1 were 1.57 (0.88-2.80) and 2.30 (1.28-4.14), respectively. After adjusting for confounding variables, the OR with a 95% CI for WMH in the T2 and T3 groups vs. the referent T1 were 1.55 (0.76-3.13) and 2.27 (1.06-4.84), respectively. CONCLUSION: AIP is independently and positively associated with WMH in a healthy population.

Vascular risk profile and white matter hyperintensity volume among Mexican Americans and non-Hispanic Whites: The HABLE study.

INTRODUCTION: Among vascular risk factors we hypothesized that an increased prevalence of diabetes in Hispanics would be associated with greater white matter hyperintensity (WMH) volume, which may contribute to cognitive decline. METHODS: A total of 1318 participants (60% female; 49% Hispanic, 51% non-Hispanic White; age 66.2 ± 8.9 years) underwent clinical evaluation and brain magnetic resonance imaging (MRI). WMH volume associations were assessed with age, sex, and ethnicity and then with vascular risk factors in a selective regression model. RESULTS: WMH volume was greater with older age (P < .0001), Hispanic ethnicity (P = .02), and female sex (P = .049). WMH volume was best predicted by age, diastolic blood pressure, hypertension history, hemoglobin A1c (HbA1c), white blood cell count, and hematocrit (P < .01 for all). Elevated HbA1c was associated with greater WMH volume among Hispanics (parameter estimate 0.08 ± 0.02, P < .0001) but not non-Hispanic Whites (parameter estimate 0.02 ± 0.04, P = .5). DISCUSSION: WMH volume was greater in Hispanics, which may be partly explained by increased WMH volume related to elevated HbA1c among Hispanics but not non-Hispanic Whites.

Neuropathology and genetics of cerebroretinal vasculopathies.

Cerebroretinal vasculopathy (CRV) and the related diseases hereditary endotheliopathy with retinopathy, neuropathy, and stroke (HERNS), hereditary vascular retinopathy (HVR) and hereditary systemic angiopathy (HSA) [subsequently combined as retinovasculopathy and cerebral leukodystrophy (RVCL)] are devastating autosomal-dominant disorders of early to middle-age onset presenting with a core constellation of neurologic and ophthalmologic findings. This family of diseases is linked by specific mutations targeting a core region of a gene. Frameshift mutations in the carboxyl-terminus of three prime exonuclease-1 (TREX1), the major mammalian 3' to 5' DNA exonuclease on chromosome 3p21.1-p21.3, result in a systemic vasculopathy that follows an approximately 5-year course leading to death secondary to progressive neurologic decline, with sometimes a more protracted course in HERNS. Neuropathological features include a fibrinoid vascular necrosis or thickened hyalinized vessels associated with white matter ischemia, necrosis and often striking dystrophic calcifications. Ultrastructural studies of the vessel walls often demonstrate unusual multilaminated basement membranes.